Altered inter- and intrahemispheric functional connectivity dynamics in autistic children

Abstract

Emerging evidence has associated autism spectrum disorder (ASD) with static functional connectivity abnormalities between multiple brain regions. However, the temporal dynamics of intra- and interhemispheric functional connectivity patterns remain unknown in ASD. Resting-state functional magnetic resonance imaging data were analyzed for 105 ASD and 102 demographically matched typically developing control (TC) children (age range: 7-12 years) available from the Autism Brain Imaging Data Exchange database. Whole-brain functional connectivity was decomposed into ipsilateral and contralateral functional connectivity, and sliding-window analysis was utilized to capture the intra- and interhemispheric dynamic functional connectivity density (dFCD) patterns. The temporal variability of the functional connectivity dynamics was further quantified using the standard deviation (SD) of intra- and interhemispheric dFCD across time. Finally, a support vector regression model was constructed to assess the relationship between abnormal dFCD variance and autism symptom severity. Both intra- and interhemispheric comparisons showed increased dFCD variability in the anterior cingulate cortex/medial prefrontal cortex and decreased variability in the fusiform gyrus/inferior temporal gyrus in autistic children compared with TC children. Autistic children additionally showed lower intrahemispheric dFCD variability in sensorimotor regions including the precentral/postcentral gyrus. Moreover, aberrant temporal variability of the contralateral dFCD predicted the severity of social communication impairments in autistic children. These findings demonstrate altered temporal dynamics of the intra- and interhemispheric functional connectivity in brain regions incorporating social brain network of ASD, and highlight the potential role of abnormal interhemispheric communication dynamics in neural substrates underlying impaired social processing in ASD.

Keywords: autism spectrum disorder; dynamic functional connectivity; interhemisphere; intrahemisphere; resting-state functional magnetic resonance imaging.

Figure 1

Average dynamic functional connectivity density (dFCD) variance for autism and typically developing controls (TC) children [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Between‐group differences for global, contralateral and ipsilateral dFCD variance. ACC, anterior cingulate cortex; ASD, autism spectrum disorder; dFCD, dynamic functional connectivity density; ES, Cohen's d effect size; FG, fusiform gyrus; ITG, inferior temporal gyrus; mPFC, medial prefrontal cortex; PostCG, postcentral gyrus; PreCG, precentral gyrus; TC, typically developing controls; TPOmid, middle temporal pole [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

Relationships between abnormal contralateral dynamic functional connectivity density (dFCD) variance and autism symptom severity. (a) Voxel‐level weightings in prediction analysis of Autism Diagnostic Observation Schedule (ADOS) communication subscore. (b) Relationships between ADOS communication subscore and predicted scores using abnormal contralateral dFCD variance (r = .36, p = .006) [Color figure can be viewed at http://wileyonlinelibrary.com]